HLA-B⁎27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope

Background & Aims: HLA-B⁄27 is associated with spontaneous HCV genotype 1 clearance. HLA-B⁄27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B⁄27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B⁄27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope. Methods: Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B⁄27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B⁄27:02 and 05. Results: The NS5B2820 epitope is only restricted by the HLA-B⁄27 subtype HLA-B⁄27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B⁄27 subtype B⁄27:05. Indeed, the epitope is very dominant in HLA-B⁄27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B⁄27:02+ chronically infected patients. Conclusions: The NS5B2820 epitope is immunodominant in the context of HLA-B⁄27:02, but is not restricted by other HLA-B⁄27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines.

Relaxing hydrotherapy WATSU (WaterShiatsu) and its effects in third trimester of pregnancy

Background WATSU (WaterShiatsu) is a bodywork-technique comprising buoyancy, passive stretches, massage, and acupressure that is administered in 35° C warm water. WATSU is believed to exert beneficial effects on pregnancy-related complaints. We conducted a pilot study to test the hypothesis that WATSU treatment during pregnancy can affect low back pain, everyday stress perception, quality of life, tonus of the uterus, amount of amniotic fluid, spontaneous course of breech presentations, and the success rate of external cephalic versions. Methods Healthy women with singleton pregnancies at gestational week 36 were included in our cohort control pilot trial. Participants in the treatment group (n = 8) received a standardized WATSU-treatment on their first and fourth day of study participation, while participants in the control group were in a waiting condition. Participants underwent ultrasound investigations and completed quantitative and qualitative questionnaires before and after intervention, as well as weekly until birth. Results In contrast to the control group, participants in the WATSU-treatment group reported significant relief of low back pain and stress. After WATSU treatment spontaneous version out of breech position occurred once in seven cases, and external cephalic version was successful in two out of three cases. As qualitative data indicate, WATSU was appreciated as a deep relaxing and enjoyable treatment method. No negative side-effects or adverse events were reported. Conclusion The findings from our pilot-study support the notion that WATSU might yield therapeutic benefits for pregnant women and warrant further research.

The new bern PET cyclotron, its research beam line, and the development of an innovative beam monitor detector

The new Bern cyclotron laboratory aims at industrial radioisotope production for PET diagnostics and multidisciplinary research by means of a specifically conceived beam transfer line, terminated in a separate bunker. In this framework, an innovative beam monitor detector based on doped silica and optical fibres has been designed, constructed, and tested. Scintillation light produced by Ce and Sb doped silica fibres moving across the beam is measured, giving information on beam position, shape, and intensity. The doped fibres are coupled to commercial optical fibres, allowing the read-out of the signal far away from the radiation source. This general-purpose device can be easily adapted for any accelerator used in medical applications and is suitable either for low currents used in hadrontherapy or for currents up to a few μA for radioisotope production, as well as for both pulsed and continuous beams.

The impact of the position effect on the factorial structure of the Culture Fair Test (CFT)

The Culture Fair Test (CFT) is a psychometric test of fluid intelligence consisting of four subtests; Series, Classification, Matrices, and Topographies. The four subtests are only moderately intercorrelated, doubting the notion that they assess the same construct (i.e., fluid intelligence). As an explanation of these low correlations, we investigated the position effect. This effect is assumed to reflect implicit learning during testing. By applying fixed-links modeling to analyze the CFT data of 206 participants, we identified position effects as latent variables in the subtests; Classification, Matrices, and Topographies. These position effects were disentangled from a second set of latent variables representing fluid intelligence inherent in the four subtests. After this separation of position effect and basic fluid intelligence, the latent variables representing basic fluid intelligence in the subtests Series, Matrices, and Topographies could be combined to one common latent variable which was highly correlated with fluid intelligence derived from the subtest Classification (r=.72). Correlations between the three latent variables representing the position effects in the Classification, Matrices, and Topographies subtests ranged from r=.38 to r=.59. The results indicate that all four CFT subtests measure the same construct (i.e., fluid intelligence) but that the position effect confounds the factorial structure

The imaging and dosimetric capabilities of a CT/MR-suitable, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer

Introduction. Investigations into the shortcomings of current intracavitary brachytherapy (ICBT) technology has lead us to design an Anatomically Adaptive Applicator (A3). The goal of this work was to design and characterize the imaging and dosimetric capabilities of this device. The A3 design incorporates a single shield that can both rotate and translate within the colpostat. We hypothesized that this feature, coupled with specific A3 component construction materials and imaging techniques, would facilitate artifact-free CT and MR image acquisition. In addition, by shaping the delivered dose distribution via the A3 movable shield, dose delivered to the rectum will be less compared to equivalent treatments utilizing current state-of-the-art ICBT applicators. ^ Method and materials. A method was developed to facilitate an artifact-free CT imaging protocol that used a "step-and-shoot" technique: pausing the scanner midway through the scan and moving the A 3 shield out of the path of the beam. The A3 CT imaging capabilities were demonstrated acquiring images of a phantom that positioned the A3 and FW applicators in a clinically-applicable geometry. Artifact-free MRI imaging was achieved by utilizing MRI-compatible ovoid components and pulse-sequences that minimize susceptibility artifacts. Artifacts were qualitatively compared, in a clinical setup. For the dosimetric study, Monte-Carlo (MC) models of the A3 and FW (shielded and unshielded) applicators were validated. These models were incorporated into a MC model of one cervical cancer patient ICBT insertion, using 192Ir (mHDR v2 source). The A3 shield's rotation and translation was adjusted for each dwell position to minimize dose to the rectum. Superposition of dose to rectum for all A3 dwell sources (4 per ovoid) was applied to obtain a comparison of equivalent FW treatments. Rectal dose-volume histograms (absolute and HDR/PDR biologically effective dose (BED)) and BED to 2 cc (BED2cc ) were determined for all applicators and compared. ^ Results. Using a "step-and-shoot" CT scanning method and MR compliant materials and optimized pulse-sequences, images of the A 3 were nearly artifact-free for both modalities. The A3 reduced BED2cc by 18.5% and 7.2% for a PDR treatment and 22.4% and 8.7% for a HDR treatment compared to treatments delivered using an uFW and sFW applicator, respectively. ^ Conclusions. The novel design of the A3 facilitated nearly artifact-free image quality for both CT and MR clinical imaging protocols. The design also facilitated a reduction in BED to the rectum compared to equivalent ICBT treatments delivered using current, state-of-the-art applicators. ^

Development of a standard sign-out procedure for clinicians in a pediatric intensive care unit

Background: Poor communication among health care providers is cited as the most common cause of sentinel events involving patients. Sign-out of patient data at the change of clinician shifts is a component of communication that is especially vulnerable to errors. Sign-outs are particularly extensive and complex in intensive care units (ICUs). There is a paucity of validated tools to assess ICU sign-outs. ^ Objective: To design a valid and reliable survey tool to assess the perceptions of Pediatric ICU (PICU) clinicians about sign-out. ^ Design: Cross-sectional, web-based survey ^ Setting: Academic hospital, 31-bed PICU ^ Subjects: Attending faculty, fellows, nurse practitioners and physician assistants. ^ Interventions: A survey was designed with input from a focus group and administered to PICU clinicians. Test-retest reliability, internal consistency and validity of the survey tool were assessed. ^ Measurements and Main Results: Forty-eight PICU clinicians agreed to participate. We had 42(88%) and 40(83%) responses in the test and retest phases. The mean scores for the ten survey items ranged from 2.79 to 3.67 on a five point Likert scale with no significant test-retest difference and a Pearson correlation between pre and post answers of 0.65. The survey item scores showed internal consistency with a Cronbach's Alpha of 0.85. Exploratory factor analysis revealed three constructs: efficacy of sign-out process, recipient satisfaction and content applicability. Seventy eight % clinicians affirmed the need for improvement of the sign-out process and 83% confirmed the need for face- to-face verbal sign-out. A system-based sign-out format was favored by fellows and advanced level practitioners while attendings preferred a problem-based format (p=0.003). ^ Conclusions: We developed a valid and reliable survey to assess clinician perceptions about the ICU sign-out process. These results can be used to design a verbal template to improve and standardize the sign-out process.^

Grain size distribution of Oligocene and Miocene sediments from the Indus Fan

The Owen Ridge south of Oman represents oceanic crust that was uplifted by compressional tectonic forces in the early Miocene. Build-out of the Indus Fan led to deposition of a thick sequence of turbidites over the site of the Ridge during the late Oligocene and early Miocene. Early Miocene uplift of the Ridge led to a pelagic cap of nannofossil chalks. Two short sequences of turbidites from the pre- and syn-uplift phases were chosen for detailed grain size analysis. The upper Oligocene section at Site 731 is composed of thin (centimeter-decimeter scale) graded mud turbidites separated by relatively thick (decimeter-meter scale) intervals of homogeneous, non-bioturbated clayey siltstones. These finer intervals are unusually silt-rich (about 60%) for ungraded material and were probably deposited as undifferentiated muds from a series of turbidity current tails. By contrast, the lower Miocene section at Site 722 is comprised of a sequence of interbedded turbidites and hemipelagic carbonates. Sharp-based silt turbidites are overlain by burrow-mottled marly nannofossil chalks. The Oligocene sequence may have accumulated in an overbank setting on the middle fan - the local topographic position favoring frequent deposition from turbidity current tails and occasional deposition from the body of a turbidity flow. Uplift of the Ridge in the early Miocene led to pelagic carbonate deposition interrupted only by turbidity currents capable of overcoming a topographic barrier. Further uplift eventually led to entirely pelagic carbonate deposition.

Composition of rocks and minerals from the Bolshoy Lyakhovsky Island (New Siberian Islands)

In the southeast of the Bolshoi Lyakhovsky Island there are outcrops of tectonic outliers composed of low-K medium-Ti tholeiitic basic rocks represented by low altered pillow basalts, as well as by their metamorphosed analogs: amphibolites and blueschists. The rocks are depleted in light rare-earth elements and were melted out of a depleted mantle source enriched in Th, Nb, and Zr also contributed to the rock formation. The magma sources were not affected by subduction-related fluids or melts. The rocks were part of the Jurassic South Anyui ocean basin crust. The blueschists are the crust of the same basin submerged beneath the more southern Anyui-Svyatoi Nos arc to depth of 30-40 km. Pressure and temperature of metamorphism suggest a setting of "warm" subduction. Mineral assemblages of the blueschists record time of a collision of the Anyui-Svyatoi Nos island arc and the New Siberian continental block expressed as a counter-clockwise PT trend. The pressure jump during the collision corresponds to heaping of tectonic covers above the zone of convergence 12 km in total thickness. Ocean rocks were thrust upon the margin of the New Siberian continental block in late Late Jurassic - early Early Cretaceous and mark the NW continuation of the South Anyui suture, one of the main tectonic sutures of the Northeastern Asia.

Age models and sea-surface paleotemperature reconstruction of sediment cores from the eastern equatorial Atlantic

Based on the faunal record of planktonic foraminifers in three long gravity sediment cores from the eastern equatorial Atlantic, the sea-surface temperature history ove the last 750,000 years was studied at a resolution of 3,000 to 10,000 years. Detailed oxygen-isotope and paleomagnetic stratigraphy helped to identify the following major faunal events: Globorotaloides hexagonus and Globorotalia tumida flexuosa became extinct in the eastern tropical Atlantic at the isotope stage 4/5 boundary, now dated at 68,000 years B.P. The persistent occurrence of the pink variety of Globigerinoides ruber started during the late stage 12 at 410,000 years B.P. CARTUNE-age. This datum may provide an easily detectible faunal stratigraphic marker for the mid-Brunhes Chron. The updated scheme of the Ericson zones helped the recognition of a hiatus at the northwestern slope of the Sierra Leone Basin covering oxygen-isotope stages 10 to 12. Classifying the planktonic foraminifer counts into six faunal assemblages, according to the factor analysis derived model of Pflaumann (1985), the tropical and the tropical-upwelling communities account for 57 % at Site 16415, and 86 % at Site 13519, respectively of the variance of the faunal record. A largely continuous paleotemperature record for both winter and summer seasons was obtained from the top of the Sierra Leone Rise with the winter temperatures ranging between 20 and 25 °C, and the summer ones between 24 and 30 °C. The record of cores from greater water depths is frequently interrupted by samples with no-analogue faunal communities and/or poor preservation. Based on the seasonality signal, during cold periods the termal equator shifted to a geographically mnore asymmetrical northern position. Dissolution altering the faunal communities becomes stronger with greater water depth, the estimated mean minimum loss of specimens increases from 70 % to 80 % between 2,860 and 3,850 water depth although some species will be more susceptible than others. Enhanced dissolution occured during stage 4 but also during cold phases in the warm stage 7 and 9. Correlations between the Foraminiferal Dissolution Index and the estimated sea-surface temperatures are significant. Foraminiferal flux rates, negatively correlated to the flux rates of organic carbon and of diatoms, may be a result of enhanced dissolution during cold stages, destroying still more of the faunal signal than indicated by the calculated minimum loss. The fluctuations of the oxygen-isotope curves and the hibernal sea-surfave temperatures are fairly coherent. During warm oxygen-isotope stages the temperature maxima lag often by 5 to 15 ka behind the respective sotope minima. During cold stages, sea-surface temperature changes are partly out of phase and contain additional fluctuations.

Perfect imaging of point sources with positive refraction

The capability of a device called the Spherical Geodesic Waveguide (SGW) to produce images with details below the classic Abbe diffraction limit (super-resolution) is analyzed here. The SGW is an optical system equivalent (by means of Transformation Optics) to the Maxwell Fish Eye (MFE) refractive index distribution. Recently, it has been claimed that the necessary condition to get super-resolution in the MFE and the SGW is the use of a Perfect Point Drain (PPD). The PPD is a punctual receptor placed in the focal point that absorbs the incident wave, without reflection or scattering. A microwave circuit comprising three elements, the SGW, the source and the drain (two coaxial lines loaded with specific impedances) is designed and simulated in COMSOL. The super-resolution properties have been analyzed for different position of the source and drain and for two different load impedances: the PPD and the characteristic line impedance. The results show that in both cases super-resolution occurs only for discrete number of frequencies. Out of these frequencies, the SGW does not show SR in the analysis carried out.

Export of Carbon from Chloroplasts at Night1

Hexose export from chloroplasts at night has been inferred in previous studies of mutant and transgenic plants. We have tested whether hexose export is the normal route of carbon export from chloroplasts at night. We used nuclear magnetic resonance to distinguish glucose (Glc) made from hexose export and Glc made from triose export. Glc synthesized in vitro from fructose-6-phosphate in the presence of deuterium-labeled water had deuterium incorporated at C-2, whereas synthesis from triose phosphates caused C-2 through C-5 to become deuterated. In both tomato (Lycopersicon esculentum L.) and bean (Phaseolus vulgaris L.), Glc from sucrose made at night in the presence of deuterium-enriched water was deuterated only in the C-2 position, indicating that >75% of carbon is exported as hexoses at night. In darkness the phosphate in the cytosol was 28 mm, whereas that in the chloroplasts was 5 mm, but hexose phosphates were 10-fold higher in the cytosol than in the chloroplasts. Therefore, hexose phosphates would not move out of chloroplasts without the input of energy. We conclude that most carbon leaves chloroplasts at night as Glc, maltose, or higher maltodextrins under normal conditions.

The current state, problems and future of Germany's air and missile defence. OSW Commentary No. 105, 2013-04-10

From German point of view, air and missile defence systems are of little relevance for the protection of Germany’s territory. However, they are seen as important for conducting ‘out of area’ operations, providing military assistance to allies, and for Germany’s political and military- technical position within NATO. The Bundeswehr has been modernising its air and missile defence systems for several years. The modernisation of very short-range and short-range systems is slightly behind schedule. Plans to modernise the medium-range air and missile defence have been encountering problems since the United States decided to refrain from buying the jointly developed MEADS system. Therefore Germany is currently considering using the results of the MEADS program in the development of its own medium-range air and missile defence system, possibly in co-operation with France and Italy. Such a system would ensure protection against short-range ballistic missiles (up to 1000 km) and might become part of NATO’s ballistic missile defence, replacing the Patriot batteries which Germany is currently operating. Furthermore, Germany could expand its involvement in NATO’s ballistic missile defence in the future by buying or developing system to intercept medium- and intermediate- range ballistic missiles (up to 3000 km and 5500 km). The final decision on this matter has not yet been taken, and will be left for the successive governments of Germany to resolve. It will depend on a number of political, military and financial factors.

Russian gas industry - current condition and prospects; New regional 'in-security' system in Central Asia; Caspian oil and gas: the facts at the end of the year 2000. OSW Study 1/2001

Russian gas industry: The current condition of the gas industry is one of the most crucial factors influencing the Russian state·s functioning, internal situation and international position. Not only is gas the principal energy resource in Russia, it also subsidises other sectors of the economy. Status of the main European gas exporter strengthens also Russia's importance in the international arena. New regional in-security: Ten years have passed since the Central Asian states declared their independence, but their relationship with Russia still remains close, and the latter treats them as its exclusive zone of influence. A crucial reason for keeping Central Asia within the orbit of Moscow·s influence is the fact that Russia exercises control over the most important transport routes out of the region of raw materials for the power industry, on which the economic development of Asia depends on. But this is the only manifestation of Central Asia·s economic dependence on Russia. Moscow lacks solid economic instruments (i.e. investment input or power industry dependence) to shape the situation in the region. Caspian oil and gas: Caspian stocks of energy resources are not, and most probably will not be, of any great significance on the world scale. Nevertheless it is the Caspian region which will have the opportunity to become an oil exporter which will reduce the dependence of the European countries on Arabian oil, and which will guarantee Russia the quantities of gas which are indispensable both for meeting its internal demands and for maintaining its current level of export. For Azerbaijan, Kazakhstan and Turkmenistan, the confirmation of the existence of successive oil strata is not only an opportunity to increase income, but also an additional bargaining chip in the game for the future of the whole region. The stake in this game is the opportunity to limit the economic, and by extension the political influences of Russia in the region.

Gazprom's position on the Russian gas market weakening. OSW Commentary No. 70, 2012-02-23

As the difficulties Gazprom has faced in recent years on the European market have multiplied1, so more and more symptoms have appeared which may suggest that the company’s dominant position is deteriorating. The decision made by the Russian government in June 2011 to double the tax Gazprom has to pay on the extraction of gas, which was later approved by parliament, was the first time in many years when the company’s fiscal privileges were withdrawn. The process of Gazprom’s assets being taken over by private companies and business partners from within Vladimir Putin’s closest circle is underway. More and more frequently attempts are being made to challenge the company’s monopoly in areas of key importance for the functioning of the entire gas sector, such as Gazprom’s exclusive right to dispose of the Russian gas transportation system and its exports monopoly. Competition from independent gas producers on the domestic market is growing, and Gazprom is gradually being pushed out of some of that market’s most profitable segments (industrial clients). The emerging tendencies in the Russian gas sector derive from a number of factors – from the situation on the European gas market, through difficulties hampering the development of the sector in Russia itself, to the private interests of the current ruling class and its business partners. The plans for a structural reform of the monopoly (including isolating gas transportation system from Gazprom), presented since 2000 by the Ministry for Economic Development and since 2003 by the Russian Association of Industrialists and Entrepreneurs (RSPP), suggest a direction for the changes necessary to stimulate the sector’s development and improve the efficiency of Gazprom itself. However, the monopolist’s current business model gives the government full control over this strategic enterprise, which is a core of Putin’s concept for developing Russia as a global energy power. Despite Putin’s recent statement that he “does not rule out privatising Gazprom in the future” (made at a meeting with political scientists in Moscow on 6 February this year), any structural reform of Gazprom (and consequently, a weakening of the state’s control over it) seems unlikely in the foreseeable future. Still, the developments on the domestic market – growing pressure from other gas companies (oil corporations and independent producers) and changes on the European market2 – may result in the weakening of Gazprom’s monopoly privileges and a gradual deterioration of its special status within Russia.

Creating Stability: National Preferences and the Origins of European Monetary System. CES Germany & Europe Working Papers, No. 00.9, December 2000

This essay compares the preferences of France, Italy, and Britain on the creation of the European Monetary System in 1978-1979, especially the Exchange Rate Mechanism, which stabilised nominal exchange rates. My claim is that the different conclusions reached by the governments (France and Italy in, Britain out) cannot be explained by economic circumstances or by interests, and I elaborate an intervening institutional variable which helps explain preferences. Deducing from spatial theory that where decisionmakers `sit' on the left-right spectrum matters to their position on the EMS, I argue that domestic constitutional power-. sharing mechanisms privilege certain actors over others in a predictable and consistent way. Where centrists were in power, the government's decision was to join. Where left or right extremists were privileged, the government's decision was negative. The article measures the centrism of the governments in place at the time, and also reviews the positions taken by the national political parties in and out of government. It is intended to contribute to the growing comparativist literature on the European Union, and to the burgeoning literature on EU-member-state relations.